Recent research from C. Patrick Carroll highlights a Catch-22 in the treatment of adults with sickle cell disease. Such patients are frequently prescribed opioid pain medications to manage chronic pain and recurrent painful crises. However, research suggests that opioids can, paradoxically, increase pain sensitivity in some cases, and work by Carroll and others demonstrates that people who regularly take opioids often report more severe pain than those who don’t.

Carroll, director of psychiatric services for the Johns Hopkins Sickle Cell Center for Adults, and colleagues recently evaluated pain experiences among adult sickle cell disease patients who were prescribed long-term opioids. These participants reported significantly higher pain, fatigue and curtailed daily activities than those not taking these drugs.

The study recruited 83 people with sickle cell disease with an average age of 39; 29 patients had been prescribed daily, long-acting opioids to manage their pain. Patients completed daily electronic pain diaries for 90 days, including self-reported levels of pain, physical activity, fatigue and pain-related daily activity interference. Patients also recorded levels of pain relief and medication satisfaction.

Sickle cell patients on long-term opioid treatment reported noncrisis pain intensities that were more than three times higher than those not taking opioids. During crisis pain days, patients on long-term opioids reported 32 percent higher pain levels. Overall, patients prescribed chronic opioid therapy were more impaired, with more than three times greater pain interference and twice the fatigue on noncrisis days, and 20 percent more pain interference and 33 percent higher fatigue.

Carroll’s group also performed standard measures of pain processing, such as how intensely participants experienced unpleasant heat and pressure. They were particularly interested in central sensitization, in which the central nervous system amplifies painful sensations. Central sensitization is a potential mechanism for both chronic pain and opioid-induced hypersensitivity to pain, says Carroll. Patients on long-term opioid therapy showed higher levels of central sensitization.

In participants not on chronic opioid therapy, central sensitization levels correlated with levels of noncrisis pain; however, this correlation vanished in patients taking chronic opioids, who had higher levels of central sensitization and pain at the outset.

“We need to be careful and skeptical about giving increasing doses of opioids to patients with sickle cell disease who are in chronic pain if it isn’t effective,” Carroll says. While the work is preliminary and should not lead physicians or those with sickle cell disease to eliminate opioids from a treatment regimen, he says this suggests that the mechanisms of pain in sickle cell disease patients taking long-term opioids may be different from those who don’t take the medications.

Medication timing might play a role, he notes, since some research suggests that opioids relieve pain immediately but then cause hypersensitivity later. What’s needed next, he says, are challenge studies “to see if we can figure out exactly what causes both reduction to pain and increased pain [with opioids].”